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C5aR inhibitor blocks complement in AMD

Article

A pepidomimetic inhibitor of the receptor for C5aR (JPE1375) blocks the mechanism that draws inflammatory cells into the disease process of age-related macular degeneration (AMD). When blocked, the numbers of neutrophils and macrophages decrease substantially, and in turn, choroidal neovascularization (CNV) also decreases, according to Anthony Adamis, MD, Department of Ophthalmology & Visual Sciences, University of Illinois.

A pepidomimetic inhibitor of the receptor for C5aR (JPE1375)blocks the mechanism that draws inflammatory cells into thedisease process of age-related macular degeneration (AMD). Whenblocked, the numbers of neutrophils and macrophages decreasesubstantially, and in turn, choroidal neovascularization (CNV)also decreases, according to Anthony Adamis, MD, Department ofOphthalmology & Visual Sciences, University of Illinois at Chicago.

The inhibitor is a small molecule of only 40 µm indiameter. The formulation is stable in biologic fluids, underhigh temperatures, and with various solvents. The molecule isreleased slowly, which lowers the patient treatment burden.

"The goal is to administer this molecule no more than twice ayear," Dr. Adamis said.

The rationale for this treatment approach is to block thecomplement cascade, which raises a question over the target pointin the cascade, he said. Dr. Adamis and his group chose to blockinflammation associated with complement activation, which hasbeen seen as a component of drusen and CNV.

"The complement cascade is part of the immune system in the eyethat manages infection," he said. "By selective blockage, thenumbers of neutrophils and macrophages that can infiltrate arereduced and the CNV can be reduced by about 50%."

Sustained release of this complement inhibitor, besides reducingthe treatment burden, also should reduce the peak concentrationin the eye and serum and lengthen the duration of drug exposure,which may be beneficial in a chronic disease such as AMD.

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